JPS5826896B2 - Sesquiterpene derivatives and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel sesquiterpene derivative and a method for producing the same.

The compounds of the present invention have the general formula: (However, in the formula, R represents a hydrogen atom or an acetyl group.

), and is represented by the following compounds.

(However, in the formula, Ac represents an acetyl group.

) The above compounds are all novel compounds that have not been described in any literature and have the physical properties described in the Examples below.

The compound of the present invention is a known substance, Warbanal (War).
burgana l), and the final synthetic substance, the above-mentioned burganal, is a natural product derived from the East African plant ``Wa burgana l''.
rburgia), its structural formula has also been determined, and its physiological activity is similar to that of the night robber moth (ar.
A powerful antifeedant (an
It is known as a useful substance that acts as a tifeedant (Chem, Comm, p. 101).
3 (1976)].

The compound of the present invention is useful as an important intermediate in the next step in the total synthesis of the barhabanal.

In the above step, the starting material 7-oxoisotrimenin (7-oxoisodrimenin) is indolimenine (is), which has already been isolated as a natural product.
odrimenine) (J, Chem, Soc
6, p.

4685 (1960)] with an oxidizing agent, especially chromic acid (HoH,
Appel, etal: J, C, S, 4685 (1
960)], and the raw material indolimenin has already been completely synthesized by the present inventor as a sesquiterpene derivative derived from 1-abietic acid, and is easily available [Japanese Patent Application No. 52-38628]. (Tokuko Showa 5
6-8034)].

In addition, easily available β-ionone (β-1one)
The present inventor has also achieved that isotrimenine can be synthesized in an extremely short process from
No. 59 (Japanese Unexamined Patent Publication No. 5536441)].

To explain the above process, the starting material 7-oxisotrimenine is first induced into a ketal form, and then a ketone form, diacetate form, epoxy form, triol form, silyl form, carbonate form, alcohol form, aldehyde form, and ketal form. , the aforementioned barburganal can be synthesized by converting it into a diol form and an aldehyde form, respectively.

To explain this according to the steps, first, the starting material 7-oxisotrimenine (2) is treated with a dialcohol and an organic acid, and the ketal compound (3) is obtained in high yield by refluxing.

The obtained ketal body (3) can be reacted with a reducing reagent in an organic solvent to lead to the compound of the present invention, the ketone body (4), in high yield.

By further reacting the obtained ketone body (4) with an acetylating agent in a solvent, the compound of the present invention, diacetate body (5), can be obtained in high yield.

The epoxy compound (6) is obtained in high yield by treating the obtained diacetate compound (5) with a peroxide in the presence of an aqueous alkali solution.

The obtained epoxy body (6) is reacted with hydrazine hydrate to introduce a double bond to obtain a triol body (7).

The obtained triol body (7) can be reacted with imidazole and trialkylsilyl chloride to obtain a silyl body (8) in which the hydroxyl group of the aryl group is protected.

The obtained silyl compound (8) is refluxed with phosgene or carbonylimidazole to obtain a carbonate compound (9) in which glycol is protected with carbonate in a high yield.

By treating the obtained carbonate form (9) with an organic acid, the silyl is returned to alcohol, and the alcohol form (9) is converted into an alcohol form.
10) can be obtained quantitatively.

When the obtained alcohol compound (10) is reacted with an oxidizing agent, the aldehyde compound (11) is obtained in high yield.

By treating the obtained aldehyde with a dialcohol and an organic acid to further protect it with an acetal, an alkali-stable ketal (12) is obtained.

By treating the obtained ketal compound (12) with an alkali, diol compound (13) 6 is obtained in high yield.

The aldehyde compound (14) is obtained by reacting with an oxidizing agent below.

When the thus obtained aldehyde compound (14) is reacted with an organic acid and the obtained diol compound 03) under basic or neutral conditions, the above-mentioned barburganal α is obtained.

Barbaganal (15) synthesized in this way completely matches the physical properties of the natural product Barbaganal.

The compound of the present invention can be produced by the following method.

That is, the ketal compound (3) can be obtained in high yield by treating the 7-oxisotrimenine (2) with a dialcohol and an organic acid and refluxing it.

In this case, organic acids such as p-toluenesulfonic acid and camphorsulfonic acid are used, aromatic hydrocarbons such as benzene and toluene are used as solvents, and ethylene glycol, 1,3- Propanediol etc. can be used, especially during benzene dissolution, p
- It is preferable to use toluenesulfonic acid or ethylene glycol.

The reaction temperature and reaction time at this time are not particularly limited, but
80-150'C and 4-12 hours, respectively, are preferred.

The obtained ketal body (3) can be reacted with a reducing reagent in an organic solvent to lead to the compound of the present invention, the ketone body 4), in high yield.

In the above reaction, lithium aluminum hydride is suitably used as the reducing reagent, and ethers such as ether, dioxane, and tetrahydrofuran are used as the solvent. In particular, when lithium aluminum hydride is used in anhydrous ether, suitable.

The reaction temperature and reaction time are not particularly limited, and room temperature and 2 to 12 hours are suitable, respectively.

By further reacting the obtained ketone body (4) with an acetylating agent in a solvent, the compound of the present invention, diacetate body (5), can be obtained in high yield.

As the acetylating agent in this case, acetic anhydride-pyridine, acetyl chloride-pyridine, etc. can be used, but particularly excellent results are obtained in the case of acetic anhydride-pyridine.

In the above reaction, the reaction temperature and reaction time are not particularly limited, and particularly suitable results are obtained at room temperature for 4 to 12 hours.

EXAMPLES Below, the method for producing the compound of the present invention will be specifically explained with reference to Examples.

Reference example (±) - Acetic acid cleaning of indomenine (1) 318■ 30
Add chromic acid 4007Q to m1 and stir at 50'C for 4 hours.

After the reaction, water is added and extracted with ether, and the ether layer is washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over sodium sulfate.

Then, the solution is distilled off to obtain an oily substance 301.

This was subjected to silica gel column chromatography (Loba
rCOlumn; hexane:acetic ether=3:1) to obtain 239 ml of 7-oxisotrimenine (2).

This is further recrystallized from n-hexane-ether to obtain colorless prism crystals.

(Physical properties) Melting point: 107-109°C Elemental analysis value: (calculated value) C172,55*
H (actual value) C1 Hl Infrared absorption spectrum (CCI) (IR) 8.12 72.41 8.12 Rainbow m, 11701 1680crIL-1 Nuclear magnetic resonance spectrum (cDc13) 20.93 (Me
) (NMR) 0.97 (Me) 1.28 (Me) 7-Okitisotrimenine (2) obtained in Reference Example 25
2ml of ethylene glycol to 20cm of benzene solution of 4cm
and p-)luenesulfonic acid were processed and refluxed overnight in a Dean-Stark apparatus.

After the reaction, the benzene layer is washed with 10% aqueous sodium carbonate and saturated brine, and then dried over magnesium sulfate.

After distilling off the solvent, silica gel column chromatography (L
obar column s Hexane:acetic ether = 3: 1), ketal form (3) 281r1
Get 19.

When this is further recrystallized from n-hexane-ether,
Obtain colorless prismatic crystals.

(Physical properties) Melting point: 88.5-89.5°C Elemental analysis value: (calculated value) C169,84H18,27 (actual value) C169,82 H2S, 27 Ri■R (CC14): vmaX1760crrL-1N
MR (CDC1a): 0.88 (Me)0.9
2(Me) 1.16 (Me) ca 3.8-4.2 (m1 Ketal compound 3 obtained in Example 1) Lithium aluminum hydride 2i was added to 100 ml of an anhydrous ether solution of 3.3 P and the mixture was heated to room temperature. Stir for 2 hours and 30 minutes.

After the reaction, water and 10% HCI are added, followed by ether extraction, and the ether layer is washed with saturated brine and dried over magnesium sulfate.

When the solvent is distilled off, ketone body (4) 2960f is obtained.

(Physical properties) ■Mass spectrometry (Mass): m/e: (high resolution mass spectrometry?) 234 (M+-H2O IR (CCl4) Niji maX3400.1665
cIIL'NMR (CDCl2): o, s 8 (M
e) 0,92 (Me) 1.15 (Me) Acetic anhydride 10- is added to a pyridine solution 10- of the ketone body (4) 2.960 P obtained in Example 2 and left at room temperature for 4 hours.

After the reaction, water is added under cooling and extracted with ether. The ether layer is washed with 10% HCl, 110% Na2CO3 and saturated brine, and then washed with magnesium sulfate.

After distilling off the solvent, it was subjected to silica gel chromatography (hexane:ether-1:1) to obtain diacetate (5) 2
．． Get 550 Y.

When this is further recrystallized from n-hexane-ether,
Colorless needle-shaped crystals are obtained.

(physical properties) Melting point: 87-88・C Elemental analysis value: (calculated value) (actual value) I R (CCI4) Niji max C, 67, 83 H, 8, 39 C, 67, 89 Hl 8,36 1745.1680cIrL M.R. (CDCl2): 0.91 (Me) 0.94 (Me) 118 (Me) 2. OQ (OAc) 2.05 (OAc)

Claims (1)

[Scope of Claims] A compound represented by the formula (wherein, R represents a hydrogen atom or an acetyl group). 2. The compound according to claim 1, wherein R is a hydrogen atom. 3. The first compound of claim 1, wherein R is an acetyl group. 4 Structural formula: A general formula characterized by reacting a compound represented by the following with lithium aluminum hydride or further reacting with acetyl IJIJ: (However, in the formula, R represents a hydrogen atom or an acetyl group.) A method for producing a compound represented by 5 A compound represented by the structural formula: is reacted with a dialcohol and an organic acid to obtain a compound represented by the structural formula: and the compound is reacted with lithium aluminum hydride or further reacted with an acetylating agent. A method for producing a compound represented by the general formula (wherein, R represents a hydrogen atom or an acetyl group).